Relationship between the thickness of bronchial wall layers, emphysema score, and markers of remodeling in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease.

Abstract

INTRODUCTION Airway remodeling plays an important role in the development of chronic obstructive pulmonary disease (COPD). Imaging methods, such as computed tomography (CT) and endobronchial ultrasound (EBUS), may be useful in the assessment of structural alterations in the lungs. OBJECTIVES The aim of this study was to evaluate a relationship between the severity of emphysema assessed by chest CT, the thickness of bronchial wall layers measured by EBUS, and the markers of remodeling in bronchoalveolar lavage fluid (BALF) in patients with COPD. PATIENTS AND METHODS The study included 33 patients with COPD who underwent pulmonary function tests, emphysema score assessment by chest CT, as well as bronchofiberoscopy with EBUS in order to measure the total bronchial wall thickness and, separately, layers L1, L2, and L3-5. Selected remodeling (matrix metalloproteinase 9 [MMP-9], tissue inhibitor of metalloproteinase 1, transforming growth factor β1 [TGF-β1]) and inflammatory markers (neutrophil elastase, eosinophil cationic protein) were measured in BALF samples using an enzyme-linked immunosorbent assay. RESULTS MMP-9 levels in BALF were significantly higher in patients with very severe bronchial obstruction than in those with moderate and mild bronchial obstruction (P = 0.02), and showed a negative correlation with forced expiratory volume in 1 second (r = -0.538, P = 0.002). The thickness of L1 and L2, which histologically correspond to the mucosa, submucosa, and smooth muscle, demonstrated a positive correlation with TGF-β1 levels in BALF (r = 0.366, P = 0.046 and r = 0.425, P = 0.02) and the thickness of L1 showed a negative association with neutrophil elastase levels (r = -0.508, P = 0.004). There was no significant correlation between the analyzed markers in BALF and the emphysema score. CONCLUSIONS Significant correlations of TGF-β1 and elastase with the thickness of bronchial wall layers, and of MMP-9 with the severity of obstruction, may suggest the involvement of these markers in airway remodeling in patients with COPD.